Abstract
Objectives: Despite a reduction in the incidence and mortality rates of gastric cancer (GC), it remains the fifth most frequently diagnosed malignancy globally. A better understanding of the regulatory mechanisms involved in the progression and development of GC is important for developing novel targeted approaches for treatment. We aimed to identify a set of differentially regulated pathways and cellular, molecular, and physiological system development and functions in GC patients infected with H. pylori infection based on copy number variation (CNV) data using next-generation knowledge discovery (NGKD) methods. Methods: In this study, we used our previous CNV data derived from tissue samples from GC patients (n = 33) and normal gastric samples (n = 15) by the comparative genome hybridization (CGH) method using Illumina HumanOmni1-Quad v.1.0 BeadChip (Zenodo Accession No: 1346283). The variant effects analysis of genetic gain or loss of function in GC was conducted using Ingenuity Pathway Analysis (IPA) software. In addition, in silico validation was performed with iPathwayGuide software using high-throughput RNA sequencing (RNAseq) data (GSE83088) from GC patients. Results: We observed 213 unique CNVs in the control group, 420 unique CNVs in the GC group, and 225 common variants. We found that cancer, gastrointestinal diseases, and organismal injury and abnormalities were the three diseases or disorders that were most affected in the GC group. We also identified that the programmed cell death ligand 1 (PD-L1) cancer immunotherapy pathway, T-cell apoptosis, T-cell exhaustion, and Type 1 regulatory T-cell (Tr1 cells) specialization were dysregulated in GC patients. RNAseq data from GC patients showed that the PD-1/PD-L1 pathway was significantly upregulated in GC samples compared with controls. Conclusions: In conclusion, in the present study, we decoded differentially impacted GC-specific diseases and biological functions and pathways based on CNV data using NGKD methods that can be adopted to design personalized therapeutic approaches for patients with GC in a typical clinical milieu.